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June 15, 2009

Falsehoods, Distortions and Outright Lies in the Gene Patenting Debate

The zeitgeist has turned harshly on patenting in the U.S., perhaps nowhere as starkly as in gene patenting. Originally the subject of op-ed rants by famous authors (see "Science Fiction in The New York Times") and quixotic bills introduced by undistinguished members of Congress (see "The Continuing Threat to Gene Patenting"), the filing by the American Civil Liberties Union of a complaint against Myriad Genetics several weeks ago seems to have opened the floodgates of opposition to these patents. Thus, there have been debates on the topic on National Public Radio (see "Gene Patenting Debate Continues"), and an otherwise respectable blogger has let his pages be used by an academic with more passion than logic to present his anti-gene patenting views.

While there may be a legitimate reason to revisit the question of whether genetic material should be patent-eligible, a great deal of the anti-gene patenting debate is based on faulty premises, incorrect science, and a studied lack of appreciation of patent law as it has been applied, inter alia, to eligibility of natural products. Since any rational debate is only as good as the information it is based upon, in this post we will try to address the more flagrant inaccuracies spouted by the anti-gene patenting crowd.

Genes are a product of nature: The facts. Genes may be, but the patents claiming genes do not claim products of nature. The simple distinction is that gene claims recite that the genes are "isolated," thereby putting to rest the canard (asserted in the pages of the august New York Times by the late Michael Crichton) that a patent holder may one day ring your doorbell and ask for a royalty from you because your liver is "using" a patented gene. More importantly, no one would want to own any person's genes: it has been known for more than forty years that any particular copy of a gene in an individual in a population is likely to contain at least one polymorphism that does or could (under the right environmental conditions) affect its function. This was illustrated recently in reports of the complete diploid genomic DNA sequence of J. Craig Venter's (at left) DNA, where more than 4 million nucleotide variants were detected (see "A Complete Diploid Human Genome Reveals Some Surprises") -- included in those surprises were an extraordinary amount of genetic variation that could affect gene expression and gene products in unpredictable ways.

But there is another, more significant distinction that requires a little biology to appreciate. Genes have been described, properly, as the instructions for producing proteins. A gene encodes the amino acid sequence of a protein in a linear sequence of 3-base triplet codons that correspond in linear order to the amino acid sequence of the protein. However, in humans (and all other animals) almost all genes are interrupted by "junk" DNA that does not encode protein (or, at least, the protein the gene encodes). The entire gene, junk and coding sequence, is transcribed into RNA by the cell and then the junk pieces are "spliced out," leaving the coding sequence (termed a messenger RNA or mRNA) that is used to produce the protein. Scientists take advantage of this process to clone genes, by isolating the mRNA and converting it into a DNA molecule called complementary DNA (cDNA) which is what is cloned, sequenced, and patented. The biology is set forth schematically below:

The hallmark of what the Supreme Court has declared is patent-eligible is "anything under the sun made by man." The cDNA copies of genes that form the basis for human gene patenting are "made by man" and not products of nature because they do not exist in nature prior to being synthesized in a test tube by a scientist. If we are honest in defining what are actually "products of nature," then they must by definition be produced by nature. cDNA molecules are not.

Genes are products of nature: The law. The legal argument that "products of nature" such as "genes" are not patent-eligible proves too much, because if genes are not patentable then many other natural products cannot be, either. This includes the example given by Hans Sauer during the NPR broadcast last week, vitamin B12, which was isolated by Merck and patented in the 1930's. It also includes various antibiotics, including lincomycin that was the subject of the In re Bergy case, and any number of products isolated from crude oil, plants, animals, and even humans (see "A DNA Patenting Thought Experiment"). Indeed, there is even a chemical element, Americium, that has been the subject of a patent, because the element is unknown in nature and produced only in a nuclear reactor (and provides one embodiment of smoke detectors found in most homes). If genes are not patent-eligible, based on the fact that they are products of nature, then the patent incentive cannot exist for these "products of nature," either.

Gene patenting inhibits genetic research. In fact, a very good case can be made that the opposite is true. This is due to another distinction glossed over by the anti-gene patenting crowd: genetic information isn't patented. Patent law requires that claims be supported by a written description sufficient to enable the skilled worker to make and use the invention. For genes, this has meant that the genetic sequence is disclosed in almost all gene patents. This information can be used for any number of purposes, including sequence comparisons (which can be performed without "isolating" a gene), detecting genetic polymorphisms, and a variety of other scientific endeavors. Indeed, agricultural scientists recently reported that they paid no heed to patents encompassing their work and gene patent owners do not enforce their patents against research scientists using gene sequences for basis research. (This statement does not apply to medical scientists and institutions performing fee-for-service testing as in the Myriad case.) For example, a retrospective study of BRCA genes in archival tumor samples (contained as laboratory collections in may hospitals and departments of academic medicine) that demonstrated genetic or familial patterns of BRCA polymorphism inheritance might infringe one of the Myriad patents that are the subject of the ACLU's suit. But it would be surprising if Myriad (or any other gene patent holder) would ever try to assert these patents against this kind of genetic research. We would be interested in any instances where a gene patent owner has threatened enforcement in the absence of commercial activity. Until such time as this evidence is forthcoming (and, to be germane to the debate and support the anti-gene patenting position it would need to be widespread), there is no evidence that gene patenting has a negative effect on genetic research.

We don't need gene patents -- researchers will do it anyway. With regard to basic genetic research, this is true -- it is the corollary to the previous point, that gene patents don't inhibit genetic research. However, there is a vast gap between identifying a genetic polymorphism related to a disease, or identifying a gene that encodes a useful protein, and developing a clinically-validated test or producing a commercial biologic drug product, and that is where biotechnology companies come in. Of course, without the prospect of patent protection, investors are unlikely to provide the funding needed by start-up biotechnology companies to develop commercial embodiments of these inventions. Large corporations, both foreign and domestic, may be able to do so, but then U.S. universities and research centers become merely unpaid research and development branches of these corporations. And in view of the complexities of biotechnology products, other avenues -- trade secrets and regulatory data exclusivity being just two -- may enable such companies to keep their "monopoly" much longer than the term of a gene patent. As just one example, the menopause drug Premarin® is not patent-protected but there is no generic version available for just these types of reasons.

Genes are not patentable after In re Kubin. This assertion, made by Joshua Sarnoff, Professor of the Practice of Law at American University's Washington College of Law during the NPR debate, conflates what is patent-eligible with what is patentable, a distinction made nicely by Judge Giles Sutherland Rich in the Bergy case. There are many things that are patent-eligible that are not patentable, because the statutory requirements are different. To be patent-eligible, an invention must be a machine, manufacture, process, or composition of matter, or an improvement thereof, and (per Supreme Court precedent) cannot be a mathematical formula, an abstract idea, or a product of nature. To be patentable, on the other hand, an invention must be new, useful, and non-obvious. The Kubin case merely stands for the court's determination that merely because a gene was unknown in the prior art does not automatically mean that it should be patentable, the principle enunciated by Judge Lourie in In re Deuel based on conventional rubrics of chemical obviousness. But the decision in Kubin was based on a set of facts unlikely to have existed for most genes that have been patented, and its effects have yet to be felt. Despite Professor Sarnoff's statements, genes are not per se unpatentable after Kubin.

Gene patenting inhibits innovation. It is easy to forget today the basis for gene patenting in the past Any number of biologic drugs have been developed that, according to a recent Federal Trade Commission report, "have improved medical treatments, reduced suffering, and saved the lives of many Americans." These drugs were developed by companies that isolated the genes encoding them, including erythropoietin, human growth hormone, interferon, blood clotting Factors VIII and XI, human insulin, tissue plasminogen activator, and a host of others. The patent incentive was instrumental in supporting investment in these companies, and in developing a biotechnology industry in the U.S. that has been a world leader for 25 years. (Paradoxically, this industry arose during a time when the U.S. was popularly portrayed as being a rustbelt has-been, a modern day Great Britain, that would be left in the dustbin of history by emerging economies that were superior to our own.) The U.S. biotechnology industry has resulted in U.S. dominance in the pharmaceutical industry, to the detriment of the very European and Japanese companies poised to overtake this country economically in the past (see "The Continuing Value of Biotech Patenting"). As anyone following the debate on follow-on biologics will recognize, the need for patent protection to attract investment in what remains a fundamentally risky industry has not diminished. Patent policies abroad already permit those countries to "free-ride" on American innovation. Why should we adopt their failed policies here? And who will create the next generation of drugs based on biotechnology if we do?

Why are they lying to us? Michael Crichton did it, Lori Andrews has been known to do it, and Professor Koepsell has done it again -- the title of his book against gene patenting is "Who Owns You?" The answer is no one, of course, as explained above, but it does raise a significant question. If the case against gene patenting were so clear, logical, and in the best interests of U.S. innovation, why do its proponents always seem to intimate that somehow someone is trying to own us? It is good propaganda, of course, and it is likely that it will be defended as being merely provocative. But it doesn't advance the debate, it inhibits reasoned discussion, and it suggests (along with the studied ignorance of the facts set forth here and elsewhere) that gene patenting is just wrong somehow. Perhaps it merely vitalism, the quasi-religious notion that natural products isolated from living things are somehow different from what can be found or produced from the inorganic world. This notion was disproven more than 100 years ago by Friedrich Wohler's demonstration that urea (produced in mammalian urine) was in fact merely a chemical compound that could be produced from non-living chemicals in a laboratory.

Or maybe it is just the same contrariness that motivates some to deny evolution or other doctrines that make them uncomfortable. It may be a strain of anti-establishment rebelliousness unique to Americans (and in other contexts, part of what makes America exceptional), or maybe it is merely the window-dressing used to excuse infringement. But unless we all make our arguments based not on fear, ignorance, or dishonesty, there cannot be a real debate. The issue is too important for that.

Comments

"...and an otherwise respectable blogger has let his pages be used by an academic with more passion than logic to present his anti-gene patenting views."

Dr. Noonan, are you perhaps refering to IP Watchdog? If so, then I think that you should offer an apology. Gene has offered a forum for views that otherwise may not be developed appropriately. The Intellectual Property arena is a very nuanced one, and without vetting the opposition and allowing the interchange of discussion, understanding will not occur.

Don't get me wrong - even with such a provided forum, those who have closed their minds will not be capable of understanding or growth. I've run into that first hand while debating "software patents".

On the other hand, the forum allows the clear portrayal of arguments and indicates the boundaries of logic and emotion, thus enabling replies (like the immediate post) to add further clarity for anyone willing to approach the subject with an open and balanced mind. It is against that vetted view that the logic of your view shines ever more brightly and illuminates the map of patentability for the uninitiated (including, hopefully, the judiciary).

You have pointed out an oasis. It is up to the camel to decide whether to take advantage of the water. Thirsty minds will know what to do.

As a sometime logic and critical thinking teacher, I am disturbed that the illogic of the argument regarding alleged "isolation" continues unabated in your post above. My analogy to drawing lines on a map, "isolating" a natural geographic feature from its surrounding topography, shows that mere isolation isn't enough to arise to innovation. You also ignore the fact that organizations representing 100s of thousands of researcher have joined the Myriad suit because they know, and have experienced, the chilling effect on research these patents have caused in the US.

Moreover, I agree with Dan, above, and salute Gene for inviting my post at IPWatchdog.com. Perhaps you prefer a chorus of "amens" to each and everything you think and say, but many of us believe a healthy debate helps shake out the truth, which is something that I readily admit none of us can claim to be sole proprietors of. I, for one, am grateful for the fact that I have shifted and modified my arguments and views thanks to the reasoned and healthy debate that some sites have afforded to this very important issue.

"Blocking another biotech or a pharmaceutical company from trying to come up with a cure for disease really does block research," says Venter, "and the public loses. Why should one company say that's their unique source of biology?"

And also conveniently ignored is the fact that many, many gene patents were effectively invalidated by the new Utility and Written Description Guidelines promulgated by the USPTO back in 2001. Most of the gene patents at the time did not have the required "specific, substantial and credible" utility, or a "well-established" utility. These patents are pretty much all invalid, and will never be asserted by their owners. Many have probably been abandoned by now for failure to pay maintenance fees, but they'll still be counted as valid gene patents by the media, won't they?

"Blocking another biotech or a pharmaceutical company from trying to come up with a cure for disease really does block research," says Venter, "and the public loses. Why should one company say that's their unique source of biology?"

And this is just the whole software / troll debate, in another industry.

That's what *really* worries me about the anti-gene patenting "debate".

Finally, Kevin, my title and question "who owns you?" is not a lie and no question can be. It's quite unnecessary to suggest I have "lied" when, if you read the book you'd see, that I agree... no one "owns" us. My arguments are more nuanced and detailed than any series of blog posts or comments can be.

As for your analogy, it is flawed. The better analogy is to natural products patenting. If you can come up with a basis for denying patents to genes, while permitting natural products like taxol (isolated from yew trees) to be patented, then we can talk.

"Drawing lines on the map" is not really relevant to patenting, since at a minimum it conflates real and intellectual property. If you want to push the analogy, we draw "lines on a map" all the time, when we divide land for homes for example. And no one argues that it is somehow improper to divided the earth in this artificial way.

I am willing to have a debate, but I believe that the fundamental dishonesty and studied ignorance exhibited by those opposing gene patents makes it hard to do.

Usually, in a debate, the opponent is invited, rather than attacked without warning as you did here. My thanks to breadcrumbs for calling my attention to your post.

Nonetheless, if you don't like the geography analogies, I have others. As I suggested, reading my book would be most fair before you go accusing me of "lies." Let's look at another analogy I used in a blog comment, however.

We purify water, isolating it from impurities that are ever-present in water everywhere on earth. Does this make H2O patentable? The processes for purification would be, or processes for synthesizing it from its constituent elements would likewise be patentable. As for genes, yes we can strike out the introns, which don't code for anything, but the resulting gene still does the exact same thing as the gene in its un-purified form, which is nothing new. Here's a good explanation of why this doesn't amount to patentable subject-matter (my thanks to 6istheman for finding this):

“The underlying notion is that a scientific principle, such as that expressed in respondent’s algorithm, reveals a relationship that has always existed.

“An example of such a discovery [of a scientific principle] was Newton’s formulation of the law of universal gravitation, relating the force of attraction between two bodies, F, to their masses, m and m’, and the square of the distance, d, between their centers, according to the equation F=mm’/d^2. But this relationship always existed — even before Newton announced his celebrated law. Such ‘mere’ recognition of a theretofore existing phenomenon or relationship carries with it no rights to exclude others from its enjoyment. . . . Patentable subject matter must be new (novel), not merely heretofore unknown. There is a very compelling reason for this rule. The reason is founded upon the proposition that, in granting patent rights, the public must not be deprived of any rights that it theretofore freely enjoyed.”

P. Rosenberg, Patent Law Fundamentals, § 4, p. 13 (1975).”

Hell, if Venter can see the lack of value of gene sequence patents, I would think that attorneys would defer to his wisdom as not only a scientist, but one who got this whole mess started.

The application of the changes in written description and utility requirements is another example of how the "problem" is overstated by the anti-gene patenting folks. Dr. Zuhn may post on these aspects in a later post. And frankly, the biggest threat to gene patenting is the 20-year term and the filing dates of most of the HGP patents (circa 2000).

At issue here is patent eligibility, a much more black and white issue. And more dangerous, since it wculd preclude the entire field.

When you entitle your book "who Owns You," you are not being nuanced, you are being inflammatory (as well as trying to sell books). Don't be disingenuous - you had the courage to choose that title, have the courage to defend it.

And, David, I am not saying everything is patentable. You can compare apples to oranges all you want, but until you can come up with a distinction between genes and other natural products (having more complexity than water), you are avoiding the debate.

And, while your book was certainly included in the post, you were not a target. If you were alone in this perhaps no one would notice. But your views (and the distortions of fact and law contained in them), as well as others, cannot go unchallenged.

It's a question, with a question mark, and it's provocative. Questions cannot be lies. So, I'm asking you to defend your statement that I somehow lied. Have the courage to stand by your accusation, which is harsher than any I have ever confronted in reasoned debate, and show me where I lied. Or take it back, I think it's beneath you, sir.

It depends on how you define "lie," doesn't it? For example, the questions "Have you stopped beating your wife?," "Have your herpes outbreaks quieted down?," and "Has your dog stopped biting the kids next door?," are at best misleading when asked of people to whom the questions do not apply because they indicate that the questions do apply. "Misleading" is a polite word for "lie." So yes, a question can "be a lie."

No, those are examples of leading questions, or loaded questions. But a lie is a statement contradictory of some fact. A question might be loaded, causing the listener to leap to a conclusion, but the statement doesn't contain the mistruth. It is the listener who errs, though the questioner might have been deceitful. A question contains no fact-bearer, it seeks facts. Thus, a question can be misleading, as you say, but that isn't the same thing as a lie. Moreover, my question is a fair question, and isn't misleading, and is explicitly answered in the book in a way that Kevin would approve, though perhaps for different reasons.

My title "Who Owns You?" is answered in the book "no one." Curiously, this is Kevin's conclusion, yet he accuses me of lying, along with Chricton and Andrews.

"Lies and the Lying Liars Who Tell Them" is a curious name, the title of an Al Franken book, coming forth with a Clintonesque statement: "it depends on how you define 'lie'" I'll let those facts speak for themselves.

One wonders if David understood the two lines of Dan's post: "Excellent post, Kevin. The next time I hear someone gripe about gene patenting I'm directing them here." Dan AGREES with Kevin's post, which means, apparently, he does not agree with David's views on gene patenting.

Not all opinions are created equal. Those that are based on ignorance of the facts don't count. When one party to a "debate" that involves the understanding of non-trivial scientific principles can't even properly parse two sentences, it's clear that that party's opinion is outside the pale.

I agree with Dan's evaluation of Kevin's slam against Gene ("an otherwise respectable blogger") and his invitation to have me post a dissenting opinion at IPWatchdog -- it was his idea entirely too. Gene and I disagree, but he isn't disagreeable, and Dan, I would argue, shares that trait with Gene as he defended Gene's decision and asked Kevin to apologize for the slam. That's what I agree with, and if you cannot discern that from my post, then the fault is yours and not mine. Thank heavens that some can keep their personal animosities from infecting a discussion. It's a shame others cannot. It shows a lack of class.

Kevin and David,
There is a very strong analogy between purified and isolated naturally occurring gene sequences and maps. The originality requirement from copyright that drives most analysis of copyrights in maps also exists as a constitutional requirement in patent law. This is a critical requirement that we in patent law have overlooked. This is good news and bad news for both sides of the debate. Pro-gene patent folks will be happy to note that maps (even though they are largely copied from nature) are original to their authors and have been copyrightable from the very first copyright statute. By analogy, gene patents are original to their inventors and are likely patentable, ignoring for now Kubin's impact on late arriving gene patents. Anti-gene patent folks will happily counter that, though maps are copyrightable, the scope of the exclusive protection has always been very thin. As a result, patent law's originality requirement would allow only very thin patent protection for purified and isolated naturally occurring gene sequences (likely only exclusive rights to the actual molecule that was purified and isolated as well as copies made from it). If you are interested, these arguments are articulated in more detail in Maintaining Competition in Copying: Narrowing the Scope of Gene Patents, 41 U.C. Davis L. Rev. 177 (2005).

>>>>We purify water, isolating it from >>>>impurities that are ever-present in >>>>water everywhere on earth. Does this >>>>>make H2O patentable? The processes for >>>>>purification would be, or processes >>>>>for synthesizing it from its >>>>>>constituent elements would likewise >>>>>>be patentable. As for genes, yes we >>>>>>can strike out the introns, which >>>>>>don't code for anything, but the >>>>>resulting gene still does the exact >>>>>>same thing as the gene in its un->>>>>>purified form, which is nothing new.

Someone reading this with no background in patent law or the science involved would think this to be quite the logical argument. Instead it is just misleading and wrong.

1. Water, no matter how made, is not patentable because water is old. That is true because the water made in the new process is still structurally and functionally the same as "water".

2. With respect to striking out the introns and the resulting nucleic acid being the "the same" as the naturally occuring gene. That is simply not true. The isolaton you dismiss as having no effect, in fact makes over-expression of the protein possible in heterologous recombinant systems that is impossible with the natural gene and is also known, depending on the way it is expressed, to change the nature of the protein itself. By way of one example, you might look into the history of human interferon. The proteins themselves were described in 1957 and in subsequent years considered to be potentially quite valuable as drugs. The problem being that no one could isolate enough of the stuff to be practical.
It was not until 1982 that the cDNAs were cloned eventually giving rise to several very useful and eventually sucessful drugs. It is unlikely that any drug company would undertake such an effort absent patent protection.
(It worth noting the interferon genes I'm describing don't have introns but nonetheless the isolation of the cDNA was a substantial contribution to medicine. In addition it is not a fair statement to say that the cDNA was a product of nature, it was transformed by isolation from its essentially cryptic state in the genome to a useful tool to make a life saving medicine.)

I disagree. There is a strong analogy between genetic information and maps - indeed, before sequencing of the human genome project made the entire sequence known, genes were mapped using restriction enzymes and other tools. And this genetic information is not patented nor patentable, nor should it be.

But isolated genes are chemical compounds, actual tangible compositions of matter, and that it where they differ from maps (which are representations of tangible physical matter). So once again, we conflate information with patentable subject matter, which does not advance the debate.

Funny, Gene doesn't think I slammed him, or that I need to apologize for the post. So let's give that part of the string a rest.

I will be more impressed with the anti-gene patenting arguments if anyone would answer the challenge I posed above (and has been posed by others): distinguish genes from any other natural product.

David's water analogy is weak because, although you can purify water, you don't have to (after all, rivers, lakes and streams have always existed and used by humanity). Genes have not always been so accessible, just like most antibiotics and plant- and animal-derived drugs.

If those against gene patents want to argue that natural products should not be patented, fine. If they want to argue that genes are different, tell us why. But by merely by declaring that because genes are "natural" they should not be patentable, they are avoiding the issue.

To the extent you did not intend to be misleading, inflammatory or disingenuous in titling your book, I apologize for implying you were lying. But I think my characterization, and your title, speak for themselves.

I don't retract in any way my statements regarding the other purveyors of fearmongering in this debate. But I agree that ad hominem attack gets in the way of the debate, and I am happy to foreswear any such implication.

I believe that the process for engineering products from isolated genes is patentable, and never have I argued otherwise. That is plenty of incentive to innovate, as Venter agrees, and would protect the manner of synthesis of interferon described by ed, above. I maintain, though, that evolution has assembled the building blocks that inform the synthesis of proteins even in cDNA, since this is the useful components of the genome that are being discovered. Thus, the sequences are not "new" even though introns are struck out because they are not doing anything. This is old, prior art, developed by nature and not by man. (see, again above the selection from P. Rosenberg). We might also create new proteins this way, as is being attempted by so-called synthetic biologists, using well-known codons to create entirely new strings that assemble proteins not already found in nature. This is the hope of those now doing work in proteiomics. If they manage to create new proteins, then those substances would be patentable.

Now, using long-existing, non-new, evolved genes (with or without introns), new and useful processes can be created, such as through the creation of monoclonal means to synthesize protein utilizing genes previously created by nature, but spliced into new creatures, and these processes and unique life forms would be and are properly patentable, as I argue in my book.

As for how genes differ from other natural products: they don't. I disagree with the patents on Pasteur's yeast and that given to "synthetic" adrenaline (imagine synthetic water). The processes for synthesizing them are clearly patentable if new. But the products themselves, the substances that result from the process are not patentable in my opinion. I think that patents on the processes are enough to spur innovation, and don't result in the strange result that a product otherwise found in nature suddenly becomes protected by patents, even though nature has been doing a good job of making those products before we came up with new and inventive means of making them.

Thank you Kevin, for you apparent retraction of the term "lie." Yes, I intended to be provocative, and look, here we've had a good, long, fruitful discussion partly because of it. People of good faith can disagree and argue without resorting to calling others "liars." This is one of the virtues of civilization.

Thanks to Oskar, ed, and Kevin for steering the discussion back to issues and away from insults.

(we have conflicting statements, I guess, from Gene regarding his characterization of your view that he was "an otherwise respectable blogger" but for his requesting my post.) I'll let him sort that out if he wants, but the word "slammed" is not my "invention."

Once again, absent man's intervention, the claimed nucleic acid molecules that you are speaking of do not exist in nature. And claims directed to a process of preparing a nucleic acid molecule or a protein encoded by a nucleic acid molecule are simply not as valuable as composition of matter claims. Therefore, if a nucleic acid molecule claim satisfies each and every requirement for patentability (novelty, nonobviousness, utility, written description, etc.) why would an inventor settle for just that claim?

OK, you don't think genes should differ from other natural products with regard to patent eligibility. This is progress, because it changes your argument from "genes shouldn't be patentable" to "natural products shouldn't be patentable." Now all you have to do is explain, on legal or philosophical grounds, why a new substance isolated from nature should not be patentable (since, like genes it always existed in nature) and why the patent incentive should not exist for the most fruitful grounds for new medicines mankind has ever known.

With regard to genes and their structure, what is patented is what is claimed, and what is claimed does not exist in nature. Period. You may think this is a distinction without a difference, but again your argument is contrary to 200 years of patent law. Following your argument, because iron and other metals exist in nature, new forms of steel should not be patentable. As you might imagine, the list could go on and on.

One more, important, question. If I make a recombinant cell to produce a protein, should the recombinant cell be patentable?

Kevin,
Independent of the map analogy (I find it helpful but it is not necessary) there is a real legal argument that gene patent advocates and the courts have yet to contend with. 1) As a constitutional matter, patent claims are limited to subject matter original to the Inventor. See The Trademark Cases, 100 U.S. 82, 93-94 (1879). 2) Originality prevents exclusive rights to subject matter that was copied (whether copied from other people or from nature). 3) Purified & isolated naturally occurring gene sequences are cloned/copied from naturally occurring gDNA or mRNA; the structure of the resulting molecule is determined by using a naturally occurring molecule as a template. 4) A claim to a purified and isolated naturally occurring gene sequence is invalid as being overly broad as it claims subject matter derived from nature and is unoriginal to the patentee. (The invalidity would be most likely through section 102(f).) At best, (and it is a bit of a legal and conceptual stretch to even get there) the researcher that purifies and isolates a gene sequences can say that they are the original Inventor of their particular molecule that they have isolated and any copies made from it.

As to other types of biotech claims that depend on the purification line of cases, they may well be different from the gene patent context. In those cases, there is not the same clear argument that the patentee copied from nature. In the DNA context, the patents are filled with discussions of cloning and templates. The technical language and the specifications themselves make it clear that the resulting purified and isolated molecules have been copied. In fact, a gene sequence that codes for a protein is trivial once we have the primary sequence for the protein. What we have been interested in is not a gene sequence that codes for the protein but instead the gene sequence that some organism actually uses to produce the protein. In other words, the utility of the purified and isolated gene sequence is that the patentee has in fact copied faithfully from nature to give us the gene sequence the organism actually uses. We don’t have quite the same type of language or sense of copying in other more traditional purification cases. But I agree that we need to be careful crafting rules that provide some distinction but yet do not end up swallowing biotech claims altogether. I think originality can do that.

As I said in the piece, your argument proves too much. Under your "originality" standard, NO natural product would be patentable. If that is your position, fine, but let's not focus on gene patents (a rather small subset) but let's talk about why the next wonder drug isolated from a plant is not patentable.

As for the "faithful copying" standard, go back to the illustration in the piece - what is claimed/patented does not exist in nature. That's just a scientific fact, and pooh-poohing it doesn't change it. Indeed, patented genes show the evidence of "the hand of man" much more extensively that most other patented natural products, which are merely isolated from their natural environment and otherwise not altered at all.

So, I ask you the question I asked David upstring: is my recombinant cell encoding and expressing a heterolous gene patentable?

Kevin,
As to the recombinant cell expressing a heterlogous gene, that cell was conceived by the Inventor. They sat down and thought to themselves: 'I think plugging that p&i gene sequence into some expression system will produce a useful composition of matter.' That is invention and it was clearly conceived of by the inventor just like when our ancestors first picked up a rock, tied it to a stick with sinew and made the first hammer. All are natural products but combined they clearly constitute an invention. There is no 102(f) problem in either case. If there is a problem, it might come under 103 where the prior art should include the sequence itself because 103 prior art includes 102(f)derived prior art. (See Oddz on Products.)

Furthermore, it is irrelevant that "what is claimed/patented does not exist in nature." I don't deny that a P&I gene sequence is novel under most provisions of 102. My legal argument is based on invalidity for derivation not lack of novelty. Imagine you have some secret invention on a mousetrap that has not been otherwise disclosed (but has been abandoned suppressed and even concealed) and I derive my invention from yours. I can argue that my derived mousetrap is patentable because it is novel but that does nothing to change that fact that a patent on a derived invention is invalid under 102(f).

Yes, but there is a big difference between deriving an invention from another (which is not patentable) and producing a new form of a genetic sequence not found in nature. You may not consider that novel, but that is a patentability argument, not a patent-eligibility argument.

"Some of the earliest and biggest products in biotechnology were proteins derived directly from patented gene sequences, and these had been very valuable. For instance, Epogen, made by Amgen (nasdaq: AMGN - news - people ), was derived from a single gene sequence.

In such cases, Venter and Lander agree, gene patents are essential."

Now, you can't have your cake and eat it too. Either all genes are patentable, or no genes are patentable. And if gene patents are "essential" for making products like Epogen, then those who oppose them would be happy with the attendant suffering of those who their policies would deprive of the benefits of the drugs made using these genes.

I agree it is a patentability argument -- specifically invalidity under 102(f). I don't think the patent-eligibility arguments against gene patents are particularly strong. Either way though, I am arguing that these broad claims for purified and isolated naturally occurring gene sequences are invalid. Perhaps narrower claims could be granted even for the initial task of purifying and isolating. But if someone takes that naturally occurring sequence and conceives of a new sequence (for example modifying a naturally occurring sequence to match the preferred expression codons of some expression system) then that Inventor has created an original and likely novel sequence; there is no more 102(f) problem. (Maybe there is still a 103 problem though as explained above).

Not true, Kevin. You paint it again as a stark either/or, when I have admitted that newly created genes, as opposed to merely discovered ones, ought to be patentable.

As for cDNA, had a good talk with my wife over dinner (she's a PhD in pharmacogenomics) who learned me up good on the process for creating cDNA describing it as creating really nothing very special. mRNA codes the sequence for the cDNA, and the mRNA exists already in nature, so it's putting to use a mechanism long extant in nature to make gene sequences without the introns. She laughed at the notion that the resulting cDNA sequence was somehow inventive. The process of making cDNA might have been patentable when it was new, but it's not.

About Epogen, it is exactly the sort of product I would claim is not patentable, although the method for its manufacture could well be as it involved a recombinant process. But, Kevin, as you said before, Craig is allowed to be wrong sometimes.

You have already admitted that you don't think natural products should be patentable, and that genes fall into the "natural products" category. I respect your point of view, although I think it wrong. But you haven't answered my question: is the recombinant cell patentable?

And as for Gene, I think it's pretty clear from his post that he doesn't think he was slammed. Nor was he.

What is most unfortunate about this silly cross talk (Koepsell's policy-driven wishes versus Noonan's correct statement of the current law) is that there, among Myriad's patent holdings and licensed technology, there are plenty of really crappy claims that should never have issued, including some in the BRCA field.

This is a serious problem that everyone could agree on: garbage claims that are overly broad and grant too much to the applicant, in light of the applicant's contributions.

I'll defer to my wife in all events, given she's the scientist in this house...

I only ever said that naturally-occurring genes should not be patented, and I have argued time and again that cDNA doesn't qualify as engineered genes. And I have argued repeatedly that engineered organisms, whose genomes are modified by humans should be patentable. So, you mischaracterize me, creating a strawman argument, when you claim that I say "genes should not be patented." I never said that. One more time: Naturally occurring genes should not be patented.

BUT new genes created by humans should be patentable, and genetic engineering yields new genes and combinations of genes that do not occur in nature. I have argued that this is all fine and good.

If an organism combines genes in new, non-obvious, and useful ways, then by all means, as I have admitted numerous times and in my book as well, patent the sucker.

And thank you, "Keep it Real" for keeping it real, and cutting to a vital heart of the matter.

As a general proposition, it would surprise me if there were not overbroad claims in gene patents, as there probably are in all fields. Patenting is a human endeavor, and hence prone to error.

But I think you mistake the position taken by the good Professor and others: they think "natural" genes (their definition) should not be patentable per se. Different question, and different consequences.

Kevin mentioned Hans Sauer's analogy to vitamin B12, and while it seems clear that David Koepsell believes Merck should not have received a patent on vitamin B12 (based on his remarks concerning Epogen), other gene patenting opponents on this thread have not really addressed the issue.

Just so we're all on the same page, Merck's patent (US 2,563,794), which issued in 1951, contains the following lone claim:

1. The compound vitamin B12, an organic substance containing cobalt, together with carbon, nitrogen, hydrogen, oxygen, and phosphorus, said compound being a red crystalline substance soluble in water, methyl and ethyl alcohol and phenol, and insoluble in acetone, ether and chloroform, and exhibiting strong absorption maxima at about 2780 A., 3610 A. and 5500 A., and an L. L. D. activity of about 11,000,000 L. L. D. units per milligram.

I would be interested in how gene patenting opponents who rely on a "natural phenomenon" argument distinguish the above claim from a claim to a nucleic acid molecule that prior to a researcher's intervention, did not exist in nature. While I am not an authority on vitamin B12, it seems that the above molecule (albeit not isolated and purified to the degree required by the above claim), did exist in nature.

"Following your argument, because iron and other metals exist in nature, new forms of steel should not be patentable."

Mmmm, I do believe that new forms of steel are an amalgamation of parts existing in nature (that is, they are more complex, rather than less complex than those found in nature).

I don't think you're quite on the mark there Kev.

Regardless of that however is the overall debate. I have to say that I agree with Kev's side about patenting such vitamins and etc. as being a good thing for progress, but on the other hand, I do see it as an afront to patent practice. Specifically, you are essentially using "isolated" to make a "negative limitation". You're reciting what the structure is, but you're doing it in terms of what it is not. The courts reversed themselves on the previous barring of such claiming practice some time ago (40's? 50's? 60's? Maybe before that? I don't remember off hand) and we're still paying the price for it since. Specifically, we're paying the price in so far as things which don't really seem like they should be patentable all of a sudden become so.

In any event, you wanted someone to tell you why your genes are different from that isolated vitamin. Simple. The gene is a part of you. The vitamin is not. Or, in the case of an isolated gene outside the human body, the gene came from you and the vitamin did not.

You're right in so far as the argument subsequently flowing from this difference will be quasi-religious. And that's just how it is. It's an argument based on feelings, and how we as humans feel about ourselves and things coming from us.

One which I feel is justified.

As an aside, I should mention that I am a bit on the religious side.

David, you simply need to recognize that your argument is not well founded in so far as the law actually exists right now and that is why Kev and Gene and those like them are never going to agree with you. You're going to have to convince a judge of your position first. They're lawyers, it is how they think. And the judge is going to be a tough sell.

A wide array of naturally occurring bacterial organisms can synthesize vitamin B12, and Merck disclosed its isolation from a naturally occurring fungus, so it naturally occurs in a number of organisms -- just not in humans. Thus, I believe your statement that humans can't synthesize vitamin B12 is not relevant to the anti-gene patenting faction's "natural phenomenon" argument.

That supports the point I was making then. The point is that we hold ourselves special, above the beasts in the field. Why? No particular reason except we like to feel superior.

We're talking a quasi religious argument for a policy against patenting things which come from ourselves or make up ourselves in this instanct. This is not some logical direct argument which relates to the "natural phenomenon" controversy at all. And that is why David should only use it in the appropriate policy setting forum rather than a courtroom, where policy arguments usually fall on deaf ears.

I think for once we might agree. However, to make things perfectly clear for the gene patenting opponents out there (I'm not talking about you, 6), I believe quasi-religious arguments have no place in this debate.

I don't think humans are special, and would be happy to allow patenting of modified or engineered human genes too. I'm not an exceptionalist, and I have never raised a quasi religious or religious argument for any position ever.

And yes, I have been arguing for a public policy change, as I recognize the courts and the PTO are applying the law in a way I think is quite mistaken.

"I recognize the courts and the PTO are applying the law in a way I think is quite mistaken"

That sounds like a legal argument, not a policy argument. Again, in the abstract as applied to all isolated genes it's not very convincing, which is to say it isn't going to convince anybody who matters.

When you get tired of tilting against this windmill, why not go after Beauregard claims? Now *there's* an example of the law being misapplied (or, rather, not being applied at all).

It's a policy argument, and it's based on some precedent... but I'm afraid the wind's at my back on this one, given the recent spate of public attention, new bills proposed in the Congress, and the lawsuit. So I'll continue my Quixotic quest for a while, and fight other battles as they arise.

I don't think humans are special, and would be happy to allow patenting of modified or engineered human genes too. I'm not an exceptionalist, and I have never raised a quasi religious or religious argument for any position ever. "

That's too bad Dav, because you're not going to get anywhere with your legal arguments.

Here's a great example of supposedly objective reporting that is in fact an opinion piece that perpetuates the falsehoods and hysteria so aptly exposed in this post:

This month's ABA Journal has a cover headline that reads "Patent Pending-On You." The actual article does no better at avoiding bias as it begins thusly
"After being diagnosed with an aggressive type of breast cancer, Lisbeth Ceriani had a double mastectomy last year followed by chemotherapy that caused her hair to fall out in clumps.
Just when she thought the worst was over, she learned that some of the genes in her body that led to the cancer were patented.
Myriad Genetics, based in Salt Lake City, holds patents on two genes and their mutations that have been linked to hereditary forms of breast and ovarian cancer. As a result, the private biotech company offers the only genetic screening tests for the diseases."

Not to belittle the serious travails of cancer victims, but I found the emotional appeal (hair falling out in clumps) quite hollow and cheap. Especially insinuating that Myriad's patenting of the genes is actually worse and/or causes Lisbeth MORE pain than the chemo. Ridiculous! I would in fact accuse the author of the article of trivializing the anguish of cancer treatment.

And someone needs to explain how ripping off the Jaws tagline ("Just when you thought it was safe to go back in the water" --> "Just when she thought the worst was over") is objective, balanced reporting rather than hysteria-inciting grandstanding.

I just posted the following on the ABA site for that muckraker piece "Wrangling Genes":

A search of NCBI’s PubMed database for the term “BRCA*” returns 7915 results. This is more than twice the number of references for the gene encoding p53, possibly the most important tumor suppressor ever discovered. Sure sounds like no one’s doing research on this “friggin’ gene” to me!